The Human Genome Project has made it increasingly possible to study the biology of cells and tissues at the genetic and molecular level using high-throughput technologies. The NIH Chemical Genomics Center (NCGC) was created as part of the NIH Roadmap Molecular Libraries Initiative, to help establish a program in chemical genomics, defined as the use of small organic compounds to study gene products and pathways encoded by the genome. By providing capacities in the academic sector to identify bioactive compounds for targets, pathways, and cellular phenotypes, this program will bring the power and diversity of small-molecule screening, chemistry, and informatics to broad array of researchers attempting to determine the function of the tens of thousands of human genes encoded by the genome. Today, there are less than 500 human gene products have chemical compounds that interact with them. The NCGC, together with other centers to be funded via the extramural Molecular Libraries Screening Center Network RFA, will explore the vast majority of the human genome for which no small-molecule chemical probes have been identified. This initiative promises to significantly improve the understanding of mechanisms by which genes and their protein products function and accelerate the development of therapies for human diseases based on knowledge of the genome.